Effect of sulphated derivatives of chitosan on lipoprotein lipase activity of rabbit plasma after their intravenous injection
✍ Scribed by Shigehiro Hirano; Junko Kinugawa
- Publisher
- Elsevier Science
- Year
- 1986
- Tongue
- English
- Weight
- 322 KB
- Volume
- 150
- Category
- Article
- ISSN
- 0008-6215
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✦ Synopsis
Heparin possesses a dual biological function in preventing blood coagulation. It forms complexes with antithrombin III' and apolipoprotein C-112-", of which the latter releases lipoprotein lipase (LPL, EC 3.1.1.3) into the circulating blood. LPLreleasing activity has also been observed with some glycosaminoglycans7-9 (e.g., heparan sulphate and dermatan sulphate) and sulphated polysaccharides1n-13 (e.g. sulphated dextran and sulphated xylan). LPL catalyses the hydrolysis of the triacylglycerol moiety of lipoproteins to afford free fatty acids, which generally go into solution as complexes with plasma albumin. However, an abnormally high concentration of free fatty acids in plasma can produce several serious pathological effectsr4, especially in hemodialysis with heparin15. Therefore, new heparinoids which possess anticoagulant activity but no LPL-releasing activity are desirable.
We have describedI the anticoagulant activity of several sulphated derivatives of chitosan as analysed by activated partial thromboplastin time (APTT), and found that O-disulphated N-acetylchitosan (mol. wt., 26 x 103) exhibited 1.9-2.2 times the activity of heparin (174 units/mg). We now report on the LPL-releasing activity of some sulphated derivatives of chitosan after their intravenous injection in rabbits.
The following derivatives were prepared, N,O-sulphated chitosan (l), Osulphated N-acetylchitosan (2 and 3), O-sulphated N-hexanoylchitosan (4), Osulphated chitosan (5), and N-sulphated O-carboxymethylchitosan (6). The molecular weights of these derivatives were in the ranges of 21-26 x lo3 (1, 2,4, and 5) and Ml-245 x 103 (3 and 6). Compounds 3 and 6 were prepared from chitosan I (Flonac-N, commercial chitosan), and 1,2,4, and 5 were prepared from chitosan II (I heated with 45% NaOH in the presence of borohydride for 4 h). Compounds 2 (mol. wt., 2.5 x 103) and 3 (150 x 103) have similar structures but different molecular weights. Table I summarises the yields, specific rotations, and elemental analyses of 14. Each sulphated derivative had i.r. absorptions at 124& 1250 (S=O) and SOO-SlO cm-r (equatorial GO-S and/or C-N-S). The d.s. for N-*Dedicated to Professor N. K. Kochetkov.